JP2005524680A - ６α−フルオロステロイドの調製のための方法 - Google Patents

６α−フルオロステロイドの調製のための方法 Download PDF

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Publication number: JP2005524680A
Authority: JP; Japan
Prior art keywords: group; formula; compound; fluoro; androstane
Prior art date: 2002-03-29
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Pending

Application number

JP2003580360A

Other languages

English (en)

Japanese (ja)

Inventor

カイネッリ・ジャンフランコ

ウマニ−ロンチ・アチッレ

サンドリ・セルジオ

コンテント・ミッチェレ

ダ・コル・マルコ

Original Assignee

ファルマビオスソシエタペルアチオニ

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2002-03-29

Filing date

2003-03-31

Publication date

2005-08-18

2003-03-31 Application filed by ファルマビオスソシエタペルアチオニ filed Critical ファルマビオスソシエタペルアチオニ

2005-08-18 Publication of JP2005524680A publication Critical patent/JP2005524680A/ja

Status Pending legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 30
238000002360 preparation method Methods 0.000 title abstract description 16
239000000203 mixture Substances 0.000 claims abstract description 34
238000006243 chemical reaction Methods 0.000 claims abstract description 21
150000007530 organic bases Chemical class 0.000 claims abstract description 14
239000003960 organic solvent Substances 0.000 claims abstract description 7
150000001875 compounds Chemical class 0.000 claims description 53
125000003700 epoxy group Chemical group 0.000 claims description 24
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 17
238000006317 isomerization reaction Methods 0.000 claims description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
238000003682 fluorination reaction Methods 0.000 claims description 9
HETCEOQFVDFGSY-UHFFFAOYSA-N Isopropenyl acetate Chemical compound CC(=C)OC(C)=O HETCEOQFVDFGSY-UHFFFAOYSA-N 0.000 claims description 8
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
-1 androstane compound Chemical class 0.000 claims description 4
150000001440 androstane derivatives Chemical class 0.000 claims description 4
230000035484 reaction time Effects 0.000 claims description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
QZLYKIGBANMMBK-UGCZWRCOSA-N 5α-Androstane Chemical compound C([C@@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CCC[C@@]2(C)CC1 QZLYKIGBANMMBK-UGCZWRCOSA-N 0.000 claims description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
125000004423 acyloxy group Chemical group 0.000 claims description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
KPADFPAILITQBG-UHFFFAOYSA-N non-4-ene Chemical compound CCCCC=CCCC KPADFPAILITQBG-UHFFFAOYSA-N 0.000 claims description 3
229910052760 oxygen Inorganic materials 0.000 claims description 3
229910052717 sulfur Inorganic materials 0.000 claims description 3
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 claims description 3
KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 claims description 2
LINDOXZENKYESA-UHFFFAOYSA-N TMG Natural products CNC(N)=NC LINDOXZENKYESA-UHFFFAOYSA-N 0.000 claims description 2
238000006640 acetylation reaction Methods 0.000 claims description 2
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
230000021736 acetylation Effects 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
230000015572 biosynthetic process Effects 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
238000005160 1H NMR spectroscopy Methods 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
238000004458 analytical method Methods 0.000 description 9
239000000047 product Substances 0.000 description 8
239000002904 solvent Substances 0.000 description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
239000012363 selectfluor Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
238000004809 thin layer chromatography Methods 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
239000012025 fluorinating agent Substances 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
239000012298 atmosphere Substances 0.000 description 4
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 4
230000007935 neutral effect Effects 0.000 description 4
0 CC(C[C@@]1*)(C(C[C@@]2CC*)C3[C@@]1(*)C(C)(CCC(OC(C)=O)=C1)C1=CC3)[C@@]2(*)C(*)=O Chemical compound CC(C[C@@]1*)(C(C[C@@]2CC*)C3[C@@]1(*)C(C)(CCC(OC(C)=O)=C1)C1=CC3)[C@@]2(*)C(*)=O 0.000 description 3
239000007810 chemical reaction solvent Substances 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
239000007858 starting material Substances 0.000 description 3
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
230000003110 anti-inflammatory effect Effects 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
239000003480 eluent Substances 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
239000012467 final product Substances 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
239000005457 ice water Substances 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
238000004237 preparative chromatography Methods 0.000 description 2
238000000746 purification Methods 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
GQQZIZWLRQNWHQ-UHFFFAOYSA-N 1-fluorocyclohexa-2,4-diene-1-sulfonamide Chemical compound NS(=O)(=O)C1(F)CC=CC=C1 GQQZIZWLRQNWHQ-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
MUCRYNWJQNHDJH-OADIDDRXSA-N Ursonic acid Chemical group C1CC(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C MUCRYNWJQNHDJH-OADIDDRXSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
150000001441 androstanes Chemical class 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
150000002118 epoxides Chemical class 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
238000001914 filtration Methods 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
150000002576 ketones Chemical group 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
125000002322 perchloryl group Chemical group *Cl(=O)(=O)=O 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
239000012265 solid product Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
125000001174 sulfone group Chemical group 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/0026—Oxygen-containing hetero ring cyclic ketals
- C07J71/0031—Oxygen-containing hetero ring cyclic ketals at positions 16, 17
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J3/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom
- C07J3/005—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom the carbon atom being part of a carboxylic function
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Steroid Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

JP2003580360A 2002-03-29 2003-03-31 ６α−フルオロステロイドの調製のための方法 Pending JP2005524680A (ja)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
IT2002MI000676A ITMI20020676A1 (it)	2002-03-29	2002-03-29	Processo di preparazione di 6(alfa)-fluro steroidi
PCT/EP2003/003328 WO2003082896A2 (fr)	2002-03-29	2003-03-31	Procede de preparation de 6?-fluoro steroides

Publications (1)

Publication Number	Publication Date
JP2005524680A true JP2005524680A (ja)	2005-08-18

Family

ID=11449614

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP2003580360A Pending JP2005524680A (ja)	2002-03-29	2003-03-31	６α−フルオロステロイドの調製のための方法

Country Status (9)

Country	Link
US (1)	US20050192437A1 (fr)
EP (1)	EP1497310A2 (fr)
JP (1)	JP2005524680A (fr)
AU (1)	AU2003221537A1 (fr)
CA (1)	CA2480629A1 (fr)
IL (1)	IL164233A0 (fr)
IT (1)	ITMI20020676A1 (fr)
MX (1)	MXPA04009383A (fr)
WO (1)	WO2003082896A2 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US8049021B2 (en)	2007-03-23	2011-11-01	Dr. Reddy's Laboratories Limited	Process for the preparation of fluorotetraene
CN101838301A (zh) *	2009-10-16	2010-09-22	吴美洲	含氟甾体化合物的制备方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4093721A (en) *	1974-08-30	1978-06-06	Glaxo Laboratories Limited	Pharmaceutical compositions of 6α,9α-difluoro-androst-4-ene-17β-carboxylates and derivatives thereof
GB1514476A (en) *	1974-08-30	1978-06-14	Glaxo Lab Ltd	Alkyl and haloalkyl androst-4-ene and androsta-1,4-diene-17beta-carboxylates
FR2701262B1 (fr) *	1993-02-05	1995-03-24	Roussel Uclaf	Nouveau procédé de préparation de stéroïdes 6 alpa, 9 alpha-difluorés et nouveaus intermédiaires.
US5543417A (en) *	1994-10-21	1996-08-06	Merck & Co., Inc.	Combination method of treating acne using 4-AZA-5α-cholestan-ones and 4-AZA-5α-androstan-ones as selective 5α-reductase inhibitors with anti-bacterial, keratolytic, or anti-inflammatory agents
IT1319654B1 (it) *	2000-11-15	2003-10-23	Farmabios S R L Ora Farmabios	Processo di isomerizzazione di 6beta-fluoro steroidi neicorrispondenti 6alfa-fluoro derivati.

2002
- 2002-03-29 IT IT2002MI000676A patent/ITMI20020676A1/it unknown
2003
- 2003-03-31 MX MXPA04009383A patent/MXPA04009383A/es unknown
- 2003-03-31 EP EP03717254A patent/EP1497310A2/fr not_active Withdrawn
- 2003-03-31 CA CA002480629A patent/CA2480629A1/fr not_active Abandoned
- 2003-03-31 JP JP2003580360A patent/JP2005524680A/ja active Pending
- 2003-03-31 US US10/508,668 patent/US20050192437A1/en not_active Abandoned
- 2003-03-31 WO PCT/EP2003/003328 patent/WO2003082896A2/fr not_active Ceased
- 2003-03-31 AU AU2003221537A patent/AU2003221537A1/en not_active Abandoned
2004
- 2004-09-22 IL IL16423304A patent/IL164233A0/xx unknown

Also Published As

Publication number	Publication date
US20050192437A1 (en)	2005-09-01
EP1497310A2 (fr)	2005-01-19
CA2480629A1 (fr)	2003-10-09
WO2003082896A3 (fr)	2003-11-20
MXPA04009383A (es)	2005-01-25
ITMI20020676A1 (it)	2003-09-29
ITMI20020676A0 (it)	2002-03-29
IL164233A0 (en)	2005-12-18
AU2003221537A8 (en)	2003-10-13
WO2003082896A2 (fr)	2003-10-09
AU2003221537A1 (en)	2003-10-13

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